The Defiant made contact with the planet Meridian during an exploration mission in the Gamma Quadrant. (DS9: "Meridian")

Later in 2371, Maquis operative Thomas Riker hijacked the Defiant and used it to attack several Cardassian targets. Commander Sisko was forced to travel to Cardassia Prime with GulDukat to help track down the vessel. Although Dukat initially wanted to destroy the Defiant, he agreed to release the vessel and the Maquis crew to Starfleet custody in exchange for the Defiant's scans of the Orias system and Riker himself. After facing overwhelming opposition from Obsidian Order forces deployed from the Orias system, Riker ultimately surrendered and the Defiant was returned to DS9. (DS9: "Defiant")

Several weeks later, the Defiant was used to carry out a joint project between the governments of the Federation, Cardassia, and Bajor to establish communications between the Alpha and Gamma Quadrants. (DS9: "Destiny")

In late 2371, a Changeling posing as Federation ambassadorKrajensky sent the Defiant on a patrol mission of the Federation-Tzenkethi border. During the mission, the Changeling sabotaged the Defiant, causing it to fly out of control towards a Tzenkethi colony that was intended to be attacked; the Dominion hoped it would provoke a second war between the two powers. The crew was eventually able to regain control of the vessel and kill the Changeling. (DS9: "The Adversary")

In early 2372, the Defiant fought its way through Cardassian space against Klingon forces to bring the Detapa Council to Deep Space 9, once briefly using its tractor beam as a 'substitute' shield to protect it from enemy fire when it was forced to drop its usual shields to beam the Council to safety. (DS9: "The Way of the Warrior")

Several weeks later, the Defiant traveled to the Gamma Quadrant to meet with a Karemma starship. During the meeting, the two vessels were attacked by Jem'Hadar forces. The Defiant engaged the Jem'Hadar in the atmosphere of a gas giant and took severe damage; several of the senior officers were incapacitated. Under the command of Lieutenant CommanderWorf, the Defiant was able to destroy the Jem'Hadar ships and rescue the Karemma. (DS9: "Starship Down")

In mid-2372, Commander Worf took the Defiant to Earth to assist Captain Sisko in foiling a plot by AdmiralLeyton which would have overthrown the Federation government and established martial law. While on route, the Defiant was forced to engage the USS Lakota under the command of CaptainErika Benteen; who was operating under the assumption that the Defiant was manned by Changelings. After a prolonged battle in which both ships took significant damage (it is strongly suggested by Major Kira that the Lakota was "in even worse shape" than the Defiant), the Lakota eventually stood down when Benteen conferred with Worf and Kira about her orders to stop the Defiant. Thus, the Defiant was allowed to continue to Earth with the evidence Sisko needed to stop the coup. (DS9: "Homefront", "Paradise Lost")

The Defiant later became home to Worf, who found adapting to life on Deep Space 9 difficult. Captain Sisko gave him approval to live on the vessel so long as it did not interfere with his duties. (DS9: "Bar Association")

After an attack on DS9 by Jem'Hadar rebels, the Defiant pursued their vessel into the Gamma Quadrant. After rescuing the crew of a disabled Jem'Hadar fighter, the crews of the Defiant and the fighter worked together to destroy an Iconian gateway that was under the control of the rebels. (DS9: "To the Death")

In late 2372, the Defiant took Odo to the Founder's new homeworld where he was to be judged for killing the Krajensky changeling the previous year. The Female Changeling allowed the vessel to personally transport him to the Founder's homeworld so long as one of her pilots entered the coordinates for the planet and wiped them from the ship's memory afterwards. While the vessel was in orbit, Garak unsuccessfully attempted to use the Defiant's weapons to attack the Great Link, but he was caught and prevented from doing so by Worf. (DS9: "Broken Link")

In early 2373, the Defiant tractored a Jem'Hadar fighter captured by Captain Sisko back to Federation space. (DS9: "The Ship")

While pursuing Maquis-defector Michael Eddington, the Defiant was disabled by a cascade virus that Eddington had installed in the ship's computers during his time as DS9's Starfleet security chief. The vessel had to be towed back to DS9 by the USS Malinche. When that vessel was later disabled by the Maquis, Captain Sisko used the damaged Defiant to continue pursuing Eddington. After Sisko poisoned a Maquis planet, Eddington surrendered to Sisko and was incarcerated. (DS9: "For the Uniform")

In late 2373, the Defiant became trapped inside a temporal distortion surrounding a planet in the Gamma Quadrant. The planet was inhabited by descendants of the Defiant crew, who revealed that the vessel would crash while attempting to escape the distortion. The Defiant crew and the planets inhabitants worked to formulate a plan that would allow the Defiant to escape back into normal space, while simultaneously creating a second ship that would crash on the planet and land 200 years in the past, thus ensuring the inhabitants survival. However, it was discovered that the plan would fail and Yedrin Dax was setting up the original Defiant to crash. The crew eventually planned to allow this event to take place, but was stopped by the elder-Odo living on the surface, who changed the ship's flight plan so that it would avoid the distortion that would send them back in time. The Defiant returned to DS9 and the colonists were found to have never existed. (DS9: "Children of Time")

In an effort to stop the Dominion's military build-up in Cardassian space, Starfleet Command opted to mine the entrance to the Bajoran wormhole, a move that was virtually guaranteed to lead to war. Despite coming under fire by Dominion forces, the Defiant was able to successfully deploy the mine field and evacuate Deep Space 9's Starfleet personnel before the Dominion took control of the station. (DS9: "Call to Arms")

The Defiant was part of a search effort to look for survivors of the USS Honshu after the latter vessel was destroyed by Cardassian forces. Upon completion of that mission the ship was immediately assigned to escort a Federation troop convoy near the Badlands. (DS9: "Waltz")

Under Worf's command, the Defiant spent the next several months on convoy duty. (DS9: "Image in the Sand")

In early-2375, the Defiant made a supply run to AR-558, a planetoid in the Chin'toka system under heavy siege by the Jem'Hadar. The Defiant crew provided a small reinforcement of the planetoid and helped disable the houdinis that were plaguing the Federation troops stationed there. (DS9: "The Siege of AR-558")

La plancia della Defiant durante la Seconda Battaglia di Chin'toka

The Defiant later served as part of a search effort to look for survivors of the IKS Koraga, which had been destroyed by Dominion forces in the Badlands. The Defiant managed to recover six escape pods, but was forced to call off its search for the Koraga's captain, Worf, after only three days due to heavy Jem'Hadar patrols in the area. (DS9: "Penumbra")

The main reason for the creation of the Defiant was that Ira Steven Behr and the writers felt that the Classe Danube runabouts would not be able to protect the space station from the Dominion, and that something with more muscle was necessary. In the second season finale, "The Jem'Hadar", the Dominion had shown themselves capable of destroying a Template:Classstarship (the USS Odyssey) and it was felt that viewers would not accept the idea that the Federation's first line of defense against such a powerful enemy was three runabouts. As Behr explains, "We had all these plans for this Dominion, not so much the Dominion War yet, but the Dominion as a three-pronged attack, and what were we going to go after them with? Shuttlecrafts? You know, I mean, with the Galileo or whatever the hell those names were? You know, it just seemed ridiculous. So we needed a ship." Similarly, production designer Herman Zimmerman states, "We needed a ship that would give the writers the opportunity to have more direct conflict." (USS Defiant, DS9 Season 3 DVD special features)

Early drafts of the script of Star Trek: Primo contatto suggested that the Defiant was to be destroyed in the Battle of Sector 001. In the DVD commentary for the film, First Contact co-writer and Deep Space Nine producer Ronald D. Moore said that Deep Space Nine's Executive Producer Ira Steven Behr had seen the script and objected to the needless destruction of his ship in a story that didn't even involve the Deep Space Nine characters (apart from Worf). It would also prove to be inconvenient for the television show, so the Defiant was eventually allowed to survive the battle, and a line suggesting that the Defiant was "adrift, but salvageable" was added to clear up any ambiguity. No reference to the damage the Defiant received during the battle was ever made on Deep Space Nine (although a brief reference was made to the battle itself in "In Purgatory's Shadow", when Sisko mentions "the recent Borg attack").

Also, the game Star Trek: Legacy features a mission depicting the Defiant's shakedown cruise under the command of Lieutenant CommanderBenjamin Sisko. The ship encounters RomulanTal Shiar forces preparing to ambush T'Uerell within Federation space and despite trying to evade them, is captured. The crew and the ship are rescued by a task force led by the USS Enterprise-D.